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To explore the optimal mixing ratio and fermentation mechanism of sorghum-sudangrass and sesbania mixed silage, this study prepared silages at ratios of 10:0, 9:1, 8:2, 7:3, and 6:4 and analyzed their chemical composition, fermentation quality, and microbial characteristics on days 3, 30, and 60 of fermentation. The results showed that dry matter (DM) content gradually decreased with prolonged fermentation, with the 7:3 and 6:4 groups maintaining relatively higher mean DM content. The 6:4 and 7:3 groups have more crude protein (CP) content at D60. Water-soluble carbohydrates (WSC) decreased gradually during fermentation. In terms of fermentation quality, pH values decreased progressively and eventually stabilized. Lactic acid (LA) content accumulated over time, with the 10:0 group displaying higher NH3-N/TN content. Butyric acid was not detected in any treatment. Microbiologically, the counts of lactic acid bacteria (LAB) and yeasts gradually decreased with fermentation time, while Escherichia coli and mold were effectively suppressed. Bacterial diversity declined during fermentation, with Firmicutes being the dominant phylum. Weissella predominated in the early stage, while Pediococcus became dominant later. In conclusion, sorghum-sudangrass and sesbania mixed silage promote nutrient preservation and fermentation stability.

Water stress is a major abiotic constraint limiting the growth and productivity of alfalfa (Medicago sativa L.). To elucidate the adaptive mechanisms and identify key drought-tolerance genes, physiological measurements were integrated with multi-omics analyses of cultivar ‘Tamu 1’ under three water treatments: waterlogging (100% field water capacity), normal irrigation (80% FWC), and drought (light: 60% FWC, moderate: 40% FWC, severe: 20% FWC). Water stress markedly inhibited plant growth, induced oxidative stress, and reduced the photosynthetic capacity. Compared with waterlogging stress (DAMs: n = 71; DEGs: n = 313), drought stress resulted in a substantially greater number of differentially accumulated metabolites (DAMs, n = 1504) and differentially expressed genes (DEGs, n = 8006). Weighted gene co-expression network analysis (WGCNA) identified six key modules and ten hub genes associated with stress responses. Integrated transcriptomic and metabolomic analyses further revealed four major responsive pathways: starch and sucrose metabolism, phenylpropanoid and flavonoid metabolism, glutathione metabolism, and zeatin biosynthesis. Based on integrative criteria, including differential expression (|log2FC| ≥ 1, adjusted p < 0.05), WGCNA modules significantly associated with drought-related traits (R2 > 0.6), as well as functional annotation and protein–protein interaction (PPI) network topology, 28 candidate genes associated with drought tolerance were identified, of which six were further validated by quantitative real-time PCR (qRT-PCR). These findings highlight key metabolic pathways and regulatory modules underlying alfalfa responses to water stress and provide valuable candidate gene resources for improving drought tolerance.

Background Atherosclerosis is characterized by complex pathological processes, including endothelial dysfunction and inflammation. The underlying pathogenic mechanisms have been well elucidated; however, effective treatments are yet to be validated. Our study explored the novel application of a recognized antiviral agent, remdesivir, focusing on its impact on endothelial activation and atherosclerosis. Methods Pharmacological treatment with remdesivir significantly reduced atherosclerotic lesions in the total aorta and decreased VCAM-1 expression in aortic roots of ApoE−/− mice. Remdesivir notably attenuated ox-LDL-induced endothelial cell (EC) activation, monocyte adhesion, and ROS production. In HUVECs, TAL1 interference via siRNA significantly increased TRAF6 protein levels, which was reversed by remdesivir. Remdesivir also reduced both total and K63-linked ubiquitination of TRAF6 in HUVECs. Immunoprecipitation assays revealed diminished co-localization of the two proteins under ox-LDL treatment, but this effect was reversed by remdesivir. Importantly, ectopic adeno-associated virus (AAV)-mediated overexpression of TAL1 reduced atherosclerotic lesions and VCAM-1 expression in the aorta of ApoE−/− mice. Results In ApoE –/– mice fed with a Western diet, remdesivir greatly attenuated atherosclerosis progression. At the cellular level, remdesivir suppressed oxidative stress, THP-1 adhesion, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 via oxidized low-density lipoprotein in human umbilical vein endothelial cells. T-cell acute lymphoblastic leukemia 1 (TAL1) functions by interacting with the ubiquitin E3 ligase TNF receptor-associated factor 6 (TRAF6) to ubiquitinate TRAF6, inhibiting nuclear factor kappa B activation. Remdesivir also restored the TAL1-TRAF6 interaction and decreased endothelial activation. Endothelial-specific TAL1 over-expression in ApoE –/– mice significantly reduced aortic plaque formation. Conclusions Remdesivir impedes atherosclerosis progression by re-establishing the interaction between TAL1 and TRAF6, diminishing endothelial activation. These findings offer an innovative therapeutic approach for atherosclerosis.

This study investigated the effects of xylo-oligosaccharide (XOS) and flavomycin (FLA) on the performance and immune function of broiler chickens. A total of 150 ArborAcres broilers were randomly divided into three groups and fed for six weeks from one day of age in cascade cages. The diets of each test group were (1) a basal diet, (2) the basal diet supplemented with 2 mg/kg FLA, and (3) the basal diet supplemented with 2 mg/kg XOS. At 21 and 42 days, the growth performance index values and short-chain fatty acid (SCFA) concentrations in the cecum were quantified. Furthermore, immunoglobulin G (IgG) and plasma interleukin 2 (IL-2) as well as mRNA expression of LPS-Induced TNF-alpha Factor ( LITAF ), Toll-like receptor-5 ( TLR5 ) and interferon gamma ( IFN γ ) in the jejunum were quantified. The results showed that administration of XOS or FLA to chickens significantly improved the average daily gain. Supplementation with XOS increased acetate and butyrate in the cecum, while FLA supplementation increased propionate in the cecum. An increase in plasma IgG was observed in XOS-fed 21-day-old broilers, but FLA supplementation decreased IgG in the plasma of 42-day-old broilers and increased plasma IL-2. Furthermore, FLA or XOS supplementation downregulated mRNA expression of IFN γ , LITAF and TLR5 . The above data suggest that addition of XOS and FLA to the diet could improve the growth performance of broilers and reduce the expression of cytokine genes by stimulating SCFA.

Peptide self-assembles with bionic properties have been widely utilized for bioactive drugs and biomedical materials. Collagen mimetic peptide (CMP) gains more attention due to its unique advantages in biosecurity and function. Unfortunately, the self-assembly mechanism of CMP, particularly the effect of intermolecular forces on its self-assembly behavior and morphology, is still unrecognized. Herein, the hydrophilic glycidol (GCD) and hydrophobic Y-glycidyl ether oxypropyl trimethoxysilane (GLH) were grafted onto the side chains of CMP through the ring-opening reaction (GCD/CMP, GLH/CMP). Subsequently, the effects of hydrophilic and hydrophobic interactions on the self-assembly behavior and morphology of CMP were further studied. The results substantiated that the GCD/CMP and GLH/CMP self-assembly followed “nucleation-growth” mechanism, and the supererogatory hydrophilic and hydrophobic groups prolonged the nucleation and growth time of CMP self-assembly. Noted that the hydrophilic interaction had stronger driving effects than hydrophobic interaction on the self-assembly of CMP. The GCD/CMP and GLH/CMP self-assembles exhibited fibrous 3D network and microsphere morphology, respectively. Furthermore, the GLH/CMP self-assembles had better resistance to degradation. Consequently, the microtopography and degradation properties of CMP self-assembles could be controlled by the hydrophilic and hydrophobic interactions between CMP, which would further provide a way for subsequent purposeful design of biomedical materials.

The effect and mechanism of acetazolamide on cardiac fibrosis induced by transverse aortic constriction (TAC) were investigated. C57BL/6 mice were subjected to TAC or sham operation and then were orally gavaged with acetazolamide (20 mg/kg/day). After 4 weeks of operation, cardiac function was detected by echocardiography. Interstitial fibrosis was stained with Masson's trichrome. The expression of a-smooth muscle actin ([alpha]-SMA), collagen I, transforming growth factor-[beta]1 (TGF-[beta]1) and Smad2 were measured by western blotting. The TAC mice displayed significant cardiac dysfunction and fibrosis. The expression of [alpha]-SMA, collagen I, TGF-[beta]1 and p-Smad2 in the TAC group was higher than those in the sham group. By contrast, acetazolamide administration inhibited interstitial fibrosis, as well as improved cardiac dysfunction induced by TAC. Acetazolamide also reduced the expression of [alpha]-SMA, collagen I, TGF-[beta]1 and p-Smad2 in the TAC mice. Acetazolamide was able to attenuate cardiac fibrosis and improve cardiac dysfunction. The molecular mechanism involved in the anti-fibrotic effect of acetazolamide possibly was through inhibiting TGF-[beta]1/Smad2 signaling pathway. Key words: cardiac fibrosis, pressure overload, acetazolamide, transforming growth factor-[beta]1

The effect and mechanism of acetazolamide on cardiac fibrosis induced by transverse aortic constriction (TAC) were investigated. C57BL/6 mice were subjected to TAC or sham operation and then were orally gavaged with acetazolamide (20 mg/kg/day). After 4 weeks of operation, cardiac function was detected by echocardiography. Interstitial fibrosis was stained with Masson's trichrome. The expression of α-smooth muscle actin (α-SMA), collagen I, transforming growth factor-β1 (TGF-β1) and Smad2 were measured by western blotting. The TAC mice displayed significant cardiac dysfunction and fibrosis. The expression of α-SMA, collagen I, TGF-β1 and p-Smad2 in the TAC group was higher than those in the sham group. By contrast, acetazolamide administration inhibited interstitial fibrosis, as well as improved cardiac dysfunction induced by TAC. Acetazolamide also reduced the expression of α-SMA, collagen I, TGF-β1 and p-Smad2 in the TAC mice. Acetazolamide was able to attenuate cardiac fibrosis and improve cardiac dysfunction. The molecular mechanism involved in the anti-fibrotic effect of acetazolamide possibly was through inhibiting TGF-β1/Smad2 signaling pathway.

Depression has been well established as an independent predictor of mortality and cardiac morbidity rates in patients with coronary artery disease (CAD). Evidence has shown that single nucleotide polymorphisms located in pre-microRNA (miRNA) or mature miRNA may modify various biological processes and affect the process of carcinogenesis, and the downregulation of neuronal nitric oxide synthase 1 (NOS1) can induce depression. It has been shown that NOS1 is the target gene of miR-146a, and that the rs2910164 G/C polymorphism can downregulate the expression of miR-146a. In the present study, computational analysis was used to identify the target of miR-146a, and a luciferase reporter assay system was used to validate NOS1 as a target gene of miR-146a. In addition, U251 cells were treated with miR-146a mimics/inhibitors to verify the negative regulatory association between miR-146a and NOS1. Reverse transcription-quantitative polymerase chain reaction analysis and western blot analysis were used to estimate the mRNA expression of NOS1 and the expression of miR-146a. The results showed that the 'seed sequence' was located within the 3′-untranslated region of NOS1 by searching an online miRNA database (www.mirdb.org), and the luciferase reporter assay confirmed that NOS1 was a direct target gene of miR-146a. It was also found that the mRNA and protein expression levels of NOS1 in U251 cells treated with miR-146a mimics and NOS1 small interfering RNA were substantially downregulated, compared with cells treated with the scramble control. The cells treated with miR-146a inhibitors showed increased expression of NOS1. In addition, the presence of a minor allele of the rs2910164 polymorphism was significantly associated with risk of depression in patients with CAD. Taken together, the findings indicated a decreased risk of depression in the patients with CAD who were carriers of the miR-146a rs2910164 C allele, and this association may be attributed to its ability to compromise the expression of miR-146a, and thereby increase the expression of its target gene, NOS1.

The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in an unprecedented setback for global economy and health. SARS-CoV-2 has an exceptionally high level of transmissibility and extremely broad tissue tropism. However, the underlying molecular mechanism responsible for sustaining this degree of virulence remains largely unexplored. In this article, we review the current knowledge and crucial information about how SARS-CoV-2 attaches on the surface of host cells through a variety of receptors, such as ACE2, neuropilin-1, AXL, and antibody–FcγR complexes. We further explain how its spike (S) protein undergoes conformational transition from prefusion to postfusion with the help of proteases like furin, TMPRSS2, and cathepsins. We then review the ongoing experimental studies and clinical trials of antibodies, peptides, or small-molecule compounds with anti-SARS-CoV-2 activity, and discuss how these antiviral therapies targeting host–pathogen interaction could potentially suppress viral attachment, reduce the exposure of fusion peptide to curtail membrane fusion and block the formation of six-helix bundle (6-HB) fusion core. Finally, the specter of rapidly emerging SARS-CoV-2 variants deserves a serious review of broad-spectrum drugs or vaccines for long-term prevention and control of COVID-19 in the future.

Developing biomaterials with antimicrobial and wound‐healing activities for the treatment of wound infections remains challenging. Macrophages play non‐negligible roles in healing infection‐related wounds. In this study, a new sequential immunomodulatory approach is proposed to promote effective and rapid wound healing using a novel hybrid hydrogel dressing based on the immune characteristics of bacteria‐associated wounds. The hydrogel dressing substrate is derived from a porcine dermal extracellular matrix (PADM) and loaded with a new class of bioactive glass nanoparticles (BGns) doped with copper (Cu) and zinc (Zn) ions (Cu–Zn BGns). This hybrid hydrogel demonstrates a controlled release of Cu2+ and Zn2+ and sequentially regulates the phenotypic transition of macrophages from M1 to M2 by alternately activating nucleotide‐binding oligomerization domain (NOD) and inhibiting mitogen‐activated protein kinases (MAPK) signaling pathways. Additionally, its dual‐temporal bidirectional immunomodulatory function facilitates enhanced antibacterial activity and wound healing. Hence, this novel hydrogel is capable of safely and efficiently accelerating wound healing during infections. As such, the design strategy provides a new direction for exploring novel immunomodulatory biomaterials to address current clinical challenges related to the treatment of wound infections. The advancement of biomaterials possessing both antimicrobial and wound‐healing properties for the treatment of wound infections continues to pose a formidable challenge. The present study introduces a novel sequential immunomodulation strategy predicated on the immune characteristics of bacterial‐associated wounds. This approach employs an innovative hybrid hydrogel dressing designed to expedite the healing process of infected wounds effectively and rapidly.